Neuronal Differentiation of Human Mesenchymal Stem Cells Using Exosomes Derived from Differentiating Neuronal Cells

• Published in: PloS one Vol. 10; no. 8; p. e0135111
• Main Authors: Takeda, Yuji S, Xu, Qiaobing
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.08.2015; Public Library of Science (PLoS)
• Subjects: Amino acids; Analysis; Animals; Biomedical engineering; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Cancer; Cell differentiation; Cell Differentiation - drug effects; Cell growth; Cell Line, Tumor; Cells (biology); Culture Media, Conditioned - chemistry; Culture Media, Conditioned - pharmacology; Differentiation; DNA microarrays; Exosomes; Exosomes - chemistry; Gene Expression Profiling; Gene Expression Regulation; Genetic aspects; Growth factors; Humans; Kinases; Melanoma; Melanoma, Experimental - chemistry; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Mice; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Microscopy; miRNA; Neural stem cells; Neurogenesis; Neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Oligonucleotide Array Sequence Analysis; PC12 Cells; Pheochromocytoma cells; Physiological aspects; Primary Cell Culture; Progenitor cells; Proteins; Rats; Regeneration; Ribonucleic acid; RNA; Spinal cord injuries; Stem cells; Technology application; Tissue engineering; Transplants & implants; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0135111

Exosomes deliver functional proteins and genetic materials to neighboring cells, and have potential applications for tissue regeneration. One possible mechanism of exosome-promoted tissue regeneration is through the delivery of microRNA (miRNA). In this study, we hypothesized that exosomes derived from neuronal progenitor cells contain miRNAs that promote neuronal differentiation. We treated mesenchymal stem cells (MSCs) daily with exosomes derived from PC12 cells, a neuronal cell line, for 1 week. After the treatment with PC12-derived exosomes, MSCs developed neuron-like morphology, and gene and protein expressions of neuronal markers were upregulated. Microarray analysis showed that the expression of miR-125b, which is known to play a role in neuronal differentiation of stem cells, was much higher in PC12-derived exosomes than in exosomes from B16-F10 melanoma cells. These results suggest that the delivery of miRNAs contained in PC12-derived exosomes is a possible mechanism explaining the neuronal differentiation of MSC.